(R)-[2-(N'-tert-butoxycarbonyl-hydrazino)-ethoxy]-succinic acid dimethyl ester | 609847-50-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R)-[2-(N'-tert-butoxycarbonyl-hydrazino)-ethoxy]-succinic acid dimethyl ester
• 英文别名: dimethyl (2R)-2-[2-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]ethoxy]butanedioate
• CAS: 609847-50-9
• 化学式: C₁₃H₂₄N₂O₇
• 分子量: 320.343
• InChiKey: PRFAGQRJKUWHBS-SECBINFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  22
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (R)-[2-(N'-tert-butoxycarbonyl-hydrazino)-ethoxy]-succinic acid dimethyl ester 在 水 作用下， 反应 7.0h， 生成 [(R)-4-amino-3-oxo-morpholin-2-yl]-acetic acid methyl ester
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990
• 作为产物：
  描述：

  D-苹果酸二甲酯 在 palladium on activated charcoal sodium periodate 、 四氧化锇 、 氢气 、 N-甲基吗啉氧化物 、 silver(l) oxide 作用下， 以 四氢呋喃 、 水 、 甲苯 为溶剂， 反应 18.0h， 生成 (R)-[2-(N'-tert-butoxycarbonyl-hydrazino)-ethoxy]-succinic acid dimethyl ester
  参考文献：
  名称：

  Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex

  摘要：

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.

  DOI：

  10.1021/jm0307990

文献信息

• Synthesis and SAR of Thrombin Inhibitors Incorporating a Novel 4-Amino-Morpholinone Scaffold:  Analysis of X-ray Crystal Structure of Enzyme Inhibitor Complex
  作者：Jonas W. Nilsson、Ingemar Kvarnström、Djordje Musil、Ingemar Nilsson、Bertil Samulesson

  DOI：10.1021/jm0307990

  日期：2003.9.1

  A 4-amino-2-carboxymethyl-3-morpholinone structural motif derived from malic acid has been used to Mimic D-Phe-Pro in the thrombin inhibiting tripeptide D-Phe-Pro-Arg. The arginine in D-Phe-Pro-Arg was replaced by the more rigid P1 truncated p-amidinobenzylamine (Pab). These new thrombin inhibitors were used to probe the inhibitor binding site of alpha-thrombin. The best candidate in this series of thrombin inhibitors exhibits an in vitro IC50 of 0.130 muM. Interestingly, the stereochemistry of the 4-amino-2-carboxymethyl-3-morpholinone motif is reversed for the most active compounds compared to that of a previously reported 2-carboxymethyl-3-morpholinone series. The X-ray crystal structure of the lead inhibitor cocrystallized with alpha-thrombin is discussed.